FAM134B-Mediated ER-phagy Upregulation Attenuates AGEs-Induced Apoptosis and Senescence in Human Nucleus Pulposus Cells
| Autor: | Bingjin Wang, Yukun Zhang, Weifeng Zhang, Cao Yang, Wencan Ke, Saideng Lu, Kun Wang, Liang Ma, Hui Liu, Yu Song, Jie Lei, Rongjin Luo, Zhiwei Liao, Shuai Li, Gaocai Li |
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| Rok vydání: | 2021 |
| Předmět: |
Glycation End Products
Advanced Senescence Aging Nucleus Pulposus Article Subject Apoptosis Stimulation Biochemistry Downregulation and upregulation Glycation Autophagy medicine Humans RNA Small Interfering Cells Cultured Cellular Senescence Gene knockdown QH573-671 Chemistry Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Biology General Medicine Up-Regulation Cell biology medicine.anatomical_structure RNA Interference Cytology Reactive Oxygen Species Nucleus Intracellular Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) |
| ISSN: | 1942-0994 1942-0900 |
| DOI: | 10.1155/2021/3843145 |
| Popis: | Previous studies have established the pathogenic role of advanced glycation end products (AGEs) accumulation in intervertebral disc degeneration (IDD). Emerging evidence indicates that ER-phagy serves as a crucial cellular adaptive mechanism during stress conditions. This study is aimed at investigating the role of FAM134B-mediated ER-phagy in human nucleus pulposus (NP) cells upon AGEs treatment and exploring its regulatory mechanisms. We observed that AGEs treatment resulted in significantly increased apoptosis, senescence, and ROS accumulation in human NP cells; meanwhile, the enhanced apoptosis and senescence by AGEs treatment could be partially alleviated with the classic ROS scavenger NAC administration. Furthermore, we confirmed that FAM134B-mediated ER-phagy was activated under AGEs stimulation via ROS pathway. Importantly, it was also found that FAM134B overexpression could efficiently relieve intracellular ROS accumulation, apoptosis, and senescence upon AGEs treatment; conversely, FAM134B knockdown markedly resulted in opposite effects. In conclusion, our data demonstrate that FAM134B-mediated ER-phagy plays a vital role in AGEs-induced apoptosis and senescence through modulating cellular ROS accumulation, and targeting FAM134B-mediated ER-phagy could be a promising therapeutic strategy for IDD treatment. |
| Databáze: | OpenAIRE |
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